Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice

Introduction: Brain-derived neurotropic factor (BDNF) is expressed throughout the central nervous system and peripheral organs involved in the regulation of blood pressure, but the systemic effects of BDNF in the control of blood pressure are not well elucidated. Materials and methods: We utilized l...

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Main Authors: Zhongming Zhang, Yijing Zhang, Yan Wang, Shengchen Ding, Chenhui Wang, Li Gao, Alan Johnson, Baojian Xue
Format: Article
Language:English
Published: SAGE Publications 2019-03-01
Series:Journal of the Renin-Angiotensin-Aldosterone System
Online Access:https://doi.org/10.1177/1470320319834406
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author Zhongming Zhang
Yijing Zhang
Yan Wang
Shengchen Ding
Chenhui Wang
Li Gao
Alan Johnson
Baojian Xue
author_facet Zhongming Zhang
Yijing Zhang
Yan Wang
Shengchen Ding
Chenhui Wang
Li Gao
Alan Johnson
Baojian Xue
author_sort Zhongming Zhang
collection DOAJ
description Introduction: Brain-derived neurotropic factor (BDNF) is expressed throughout the central nervous system and peripheral organs involved in the regulation of blood pressure, but the systemic effects of BDNF in the control of blood pressure are not well elucidated. Materials and methods: We utilized loxP flanked BDNF male mice to cross with nestin-Cre female mice to generate nerve system BDNF knockdown mice, nestin-BDNF (+/–), or injected Cre adenovirus into the subfornical organ to create subfornical organ BDNF knockdown mice. Histochemistry was used to verify injection location. Radiotelemetry was employed to determine baseline blood pressure and pressor response to angiotensin II (1000 ng/kg/min). Real-time polymerase chain reaction was used to measure the expression of renin–angiotensin system components in the laminal terminalis and peripheral organs. Results: Nestin-BDNF (+/–) mice had lower renin–angiotensin system expression in the laminal terminalis and peripheral organs including the gonadal fat pad, and a lower basal blood pressure. They exhibited an attenuated hypertensive response and a weak or similar modification of renin–angiotensin system component expression to angiotensin II infusion. Subfornical organ BDNF knockdown was sufficient for the attenuation of angiotensin II-induced hypertension. Conclusion: Central BDNF, especially subfornical organ BDNF is involved in the maintenance of basal blood pressure and in augmentation of hypertensive response to angiotensin II through systemic regulation of the expression of renin–angiotensin system molecules.
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spelling doaj.art-4b9d9e921809403694c3b151c926864e2024-03-02T19:45:37ZengSAGE PublicationsJournal of the Renin-Angiotensin-Aldosterone System1752-89762019-03-012010.1177/1470320319834406Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in miceZhongming Zhang0Yijing Zhang1Yan Wang2Shengchen Ding3Chenhui Wang4Li Gao5Alan Johnson6Baojian Xue7Zhang Zhongjing College of Chinese Medicine, Henan Key Laboratory of Zhang Zhongjing’s Formulea for Immunoregulation, Nanyang Institute of Technology, ChinaZhang Zhongjing College of Chinese Medicine, Henan Key Laboratory of Zhang Zhongjing’s Formulea for Immunoregulation, Nanyang Institute of Technology, ChinaZhang Zhongjing College of Chinese Medicine, Henan Key Laboratory of Zhang Zhongjing’s Formulea for Immunoregulation, Nanyang Institute of Technology, ChinaZhang Zhongjing College of Chinese Medicine, Henan Key Laboratory of Zhang Zhongjing’s Formulea for Immunoregulation, Nanyang Institute of Technology, ChinaZhang Zhongjing College of Chinese Medicine, Henan Key Laboratory of Zhang Zhongjing’s Formulea for Immunoregulation, Nanyang Institute of Technology, ChinaZhang Zhongjing College of Chinese Medicine, Henan Key Laboratory of Zhang Zhongjing’s Formulea for Immunoregulation, Nanyang Institute of Technology, ChinaDepartment of Psychological and Brain Sciences, University of Iowa, USADepartment of Psychological and Brain Sciences, University of Iowa, USAIntroduction: Brain-derived neurotropic factor (BDNF) is expressed throughout the central nervous system and peripheral organs involved in the regulation of blood pressure, but the systemic effects of BDNF in the control of blood pressure are not well elucidated. Materials and methods: We utilized loxP flanked BDNF male mice to cross with nestin-Cre female mice to generate nerve system BDNF knockdown mice, nestin-BDNF (+/–), or injected Cre adenovirus into the subfornical organ to create subfornical organ BDNF knockdown mice. Histochemistry was used to verify injection location. Radiotelemetry was employed to determine baseline blood pressure and pressor response to angiotensin II (1000 ng/kg/min). Real-time polymerase chain reaction was used to measure the expression of renin–angiotensin system components in the laminal terminalis and peripheral organs. Results: Nestin-BDNF (+/–) mice had lower renin–angiotensin system expression in the laminal terminalis and peripheral organs including the gonadal fat pad, and a lower basal blood pressure. They exhibited an attenuated hypertensive response and a weak or similar modification of renin–angiotensin system component expression to angiotensin II infusion. Subfornical organ BDNF knockdown was sufficient for the attenuation of angiotensin II-induced hypertension. Conclusion: Central BDNF, especially subfornical organ BDNF is involved in the maintenance of basal blood pressure and in augmentation of hypertensive response to angiotensin II through systemic regulation of the expression of renin–angiotensin system molecules.https://doi.org/10.1177/1470320319834406
spellingShingle Zhongming Zhang
Yijing Zhang
Yan Wang
Shengchen Ding
Chenhui Wang
Li Gao
Alan Johnson
Baojian Xue
Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice
Journal of the Renin-Angiotensin-Aldosterone System
title Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice
title_full Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice
title_fullStr Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice
title_full_unstemmed Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice
title_short Genetic knockdown of brain-derived neurotrophic factor in the nervous system attenuates angiotensin II-induced hypertension in mice
title_sort genetic knockdown of brain derived neurotrophic factor in the nervous system attenuates angiotensin ii induced hypertension in mice
url https://doi.org/10.1177/1470320319834406
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